Riquelme was born as the eldest of 11 children in a poor family, one day before Argentina won the 1978 World Cup. He began playing football in the localities of San Fernando, playing for different local clubs, before gaining the opportunity to trial with the junior teams of Argentinos Juniors. After trialling, he was signed by the club where he began playing as a central midfielder. Boca Juniors and River Plate spotted him when he was a youth player for Argentinos Juniors. In 1995, however, Riquelme was transferred from Argentinos Juniors U-20 to Boca Juniors U-20 for a fee of US$800,000, during an operation insisted by trainer Carlos Salvador Bilardo which led to the then president of Boca Juniors, Mauricio Macri, establishing various purchases of Argentinos Juniors youth players.

On 10 November 1996, aged 18, Riquelme made his Primera División debut in a 2–0 win against Unión de Santa Fe. Two weeks later, he scored his first senior goal in a 6–0 triumph over Huracán.

In 1997, after a successful stint with Argentina’s under-20 team, Riquelme was called up to the Argentina national team by coach Daniel Passarella for their last qualifying match for the 1998 World Cup on 16 November 1997. The match was played at the stadium of Boca Juniors, La Bombonera, where a 19-year-old Riquelme debuted for Argentina when he entered the field in the last minutes of the 1–1 draw against Colombia. His first major tournament for Argentina was at the 1999 Copa América.

Riquleme was selected as captain of Argentina for the 1997 FIFA World Youth Championship and played in all three group stage matches. He scored Argentina’s third goal in the 50th minute of their 3–0 victory against Hungary on 18 June 1997. He then scored a 55th-minute winner in Argentina’s 2–1 win against Canada on 20 June 1997. In Argentina’s final group stage match, against Australia, Riquelme scored an 88th-minute penalty to level the scores at 3–3 before Australia scored a 90th-minute penalty to win the game. Argentina had gained six points and finished in second in their group, advancing to the stage of the tournament. On 26 June 1997, Argentina faced England in the round of 16, where Riquelme scored a tenth-minute penalty as Argentina claimed a 2–1 victory. Argentina went on to defeat Brazil 2–0 in the quarter-final, the Republic of Ireland 1–0 in the semi-final, and came from behind to beat Uruguay 2–1 in the final, claiming their third FIFA World Youth Championship. Riquelme had scored four goals for the tournament and Argentina were awarded with the FIFA Fair Play Award.

In May 1998, José Pékerman again included Riquelme in Argentina’s under-20 squad for the 1998 Toulon Tournament, held in France. Argentina triumphed 2–0 against France in the final as Riquelme played all five matches of the tournament and was named as Player of the Tournament.

Riquelme was included in Argentina’s 22-man squad for the 1999 Copa América in Paraguay, wearing the number 22 shirt. He was one of six Boca Juniors players selected in the squad. He played in Argentina’s opening group stage match, a 3–1 victory against Ecuador on 1 July 1999. He was replaced in the 90th minute for Diego Cagna. in Argentina’s second group stage fixture, on 4 July 1999, Riquelme played the full 90 minutes in a 3–0 loss against Colombia. On 7 July 1999, he again played the full 90 minutes in Argentina’s third group stage match, a 2–0 victory over Uruguay. Argentina finished in second place of their respective group with six points, facing Brazil in the quarter-finals on 11 July 1999. Riquelme played in the entire match of Argentina’s 2–1 defeat, having been in front 1–0 until the 32nd minute of the match.

In 2000, Riquelme participated at the 2000 CONMEBOL Men Pre-Olympic Tournament, which saw Argentina fail to qualify for the 2000 Summer Olympics. He appeared three times and scored one goal during the competition. Riquelme scored his first international goal in a 3–1 away victory during a friendly against Libya in Tripoli on 30 April 2003. On 17 November 2004, Riquelme scored his second international goal for Argentina during a 3–2 home victory in a 2006 FIFA World Cup qualification match against Venezuela. Before departing for the 2005 FIFA Confederations Cup, Riquelme scored in Argentina’s 3–1 home victory against Brazil on 8 June, during their 2006 FIFA World Cup qualifier in Buenos Aires. On 9 October 2005, Riquelme scored his seventh international goal in a 2–0 home victory against Peru during a 2006 FIFA World Cup qualification match. Riquelme scored a penalty in the 81st minute. Riquelme’s eighth international goal came in a 1–0 victory over Qatar in a friendly match in Doha on 16 November 2005.

In July 2002, after seven successful seasons with Boca Juniors which brought him and the club six major titles, including the Intercontinental Cup and the Copa Libertadores in 2000, Riquelme was transferred to Barcelona in Spain for a reported €11 million transfer fee. Shortly before his departure, his brother, Cristian, was kidnapped; Riquelme negotiated for his brother’s release and eventually paid the ransom, later stating this was one of the reasons why he chose to leave Boca.

A peculiar contract situation arose when, on 7 December 2005, Villarreal beat French club Lille 1–0 to win its Champions League group, knocking out English giants Manchester United and advancing to the knockout stages in the club’s debut season in the main continental competition. Because of a clause in the transfer contract with Barcelona, Villarreal had to pay €1 million to the Catalan club. Additionally, the contract included two other “€1 million clauses”: One if Villarreal finished in one of the top four league positions in 2005–06, and an identical clause for the following season.

On 25 April 2006, as Villarreal reached the last-four in the Champions League, in the second leg against Arsenal, Jens Lehmann saved a Riquelme penalty that would have taken the match to extra time. The game ended 0–0 at El Madrigal.

Riquelme scored his first goal of the 2006–07 season in a 3–2 home victory against Real Zaragoza on 24 September 2006. He scored a penalty in the 79th minute to give Villarreal their third goal of the match. Riquelme went on to make just 13 league appearances during the first half of the 2006–07 La Liga and played no part in the 2006–07 Copa del Rey.

In 2006, Riquelme was named captain of the Argentina national football team by new coach Alfio Basile. After a 3–0 defeat again in Brazil, Riquelme had received a lot of criticism and responsibility for the defeat. This affected the health of Riquelme’s mother, who had been hospitalized twice in two months after the 2006 World Cup, and this led to Riquelme publicly announcing his international retirement from the Argentina national team on 13 September 2006. At that point, Riquelme had made 37 international appearances and had scored eight goals. On 13 October 2007, Riquelme emerged from three months of inactivity at Villarreal to score two free-kicks in a 2–0 win against Chile to get Argentina off to a winning start in the 2010 World Cup qualifiers. On 17 November, Riquelme again netted twice in Argentina’s 3–0 home victory against Bolivia, again during a 2010 World Cup qualifier match. This brought him to a total of 17 international goals. In March 2009, Riquelme decided to retire from the national team after a disagreement with coach Diego Maradona. Former manager Sergio Batista stated he would have liked for Riquelme to return to international play, hinting at the possibility of the player appearing in a friendly with Spain in August 2010, which eventually did not happen.

Following a tense situation between player, the Villarreal board of directors and manager Manuel Pellegrini, Riquelme accepted a five-month loan back to Boca Juniors from February 2007 until 30 June 2007. He joined Boca for the 2007 Torneo Clausura of the 2007–08 Argentine Primera División season, debuting during the 2007 Torneo Clausura in a 1–1 home draw against Rosario Central on 17 February 2007. He scored his first goal for Boca – in his newest stint – in a 1–1 home draw against Independiente on 9 March 2007. He scored in the 54th minute to level the scores. His first goal of the 2007 Copa Libertadores came in Boca’s third group-stage match against Mexico’s Toluca on 22 March 2007. Riquelme scored in the 23rd minute, Boca’s second goal of the match in an eventual 3–0 home victory. Boca finished in second position of their respective group with ten points, advancing to the knockout stages of the competition.

During the knockout stages of the competition, Boca faced Vélez Sarsfield in the round of 16 fixtures. During the first leg on 2 May 2007, Riquelme scored in the first minute as Boca claimed a 3–0 home victory. Having progressed to the quarter-finals, Boca Juniors faced Paraguayan side Club Libertad. During the second-leg of the quarter-finals, played on 24 May 2007, Riquelme scored Boca’s first goal in the 61st minute of the match as they claimed a 2–0 away victory and a 3–1 aggregate result, ensuring progression to the semi-finals. During Boca’s second-leg semi-final fixture against Colombia’s Cúcuta Deportivo on 7 June 2007, Riquelme scored a 44th-minute free kick, scoring Boca’s first goal of their 3–0 home victory. After winning 4–3 on aggregate, Boca advanced to the 2007 Copa Libertadores Final, where they would face Brazilian side Grêmio in June 2007.

In August 2007, it was reported that Boca had given up hope of re-signing Riquelme. A few days later, however, the situation changed, with Boca director Juan Carlos Crespi expressing confidence in the player’s return “within 10 days”. The negotiations stalled when Villarreal’s counteroffered to sell Riquelme only in exchange for €4 million, Rodrigo Palacio and half the rights to either Mauro Boselli or Jonathan Maidana, terms which were rejected by Boca. On 30 August 2007, however, it was announced Riquelme had been signed by Atlético Madrid for a fee of €8 million, though the deal fell through at the last minute, leaving Riquelme a Villarreal player. He was given the number 16 shirt for the 2007–08 season. Then, on 26 November 2007, Riquelme reached an agreement with Villarreal to allow his re-joining Boca Juniors when the next transfer window re-opened, in January 2008.

Boca opted to pay Villarreal US$15 million to purchase Riquelme, while Villarreal would pay Riquelme’s salary on behalf of Boca Juniors for remainder of the 2007–08 playing season, which was approximately €3 million. The deal was the most expensive fee paid to an Argentine for its respective player in history. Riquelme subsequently signed a contract lasting from the end of 2007 to 2010. He was unable to participate in the 2007 FIFA Club World Cup as he was not registered by FIFA in time to be able to compete at the tournament.

On 26 June 2007, Riquelme was recalled to the national team by coach Alfio Basile as part of Argentina’s 23-man squad for 2007 Copa América. During the early morning after Boca Juniors had claimed the 2007 Copa Libertadores, Riquelme hurriedly returned to Buenos Aires and departed with the Argentina national team to Venezuela for the tournament. On 28 June, Riquelme featured in Argentina’s opening group stage match, a 4–1 victory against the United States. On 2 July, Argentina faced Colombia in their second group stage match. Riquelme netted twice, with a header in the 34th minute and then with a free-kick in the 45th minute, as Argentina won the match, 4–2.

During the entire 2007–08 Argentine Primera División season, Riquelme would only go on to make ten league appearances and score one league goal. His first match of 2007–08 came in a 1–1 draw against Rosario Central during the 2008 Torneo Clausura. On 4 May 2008, he assisted Sebastián Battaglia in scoring Boca’s only goal in their 1–0 home victory in the Superclásico with River Plate. Riquelme had taken a corner which was played to Battaglia, who headed the ball into the net in the 14th minute. During Boca’s last 2008 Copa Libertadores group-stage fixture against Maracaibo on 22 April 2008, Riquelme assisted defender Gabriel Paletta in scoring Boca’s first goal when his free-kick was played towards Paletta, who headed the ball into the net in the tenth minute. Riquelme then scored Boca’s third goal in the 74th minute with a close-ranged chip as Boca claimed a 3–0 home victory and finished in second position of their respective group, qualifying for the knockout stages of the competition.

During the first-leg of the round of 16 stage on 30 April 2008, Riquelme side footed the ball into the net in the sixth minute after receiving a pass from Álvaro González. Boca went on to win the match 2–1 and eventually claimed a 4–2 aggregate win. The club then faced Fluminense in the semi-final stages. In the first leg on 28 May 2008, Riquelme scored in the 12th minute of the match to give Boca a 1–0 lead after receiving a pass from Rodrigo Palacio, who played the ball across goal for Riquelme to convert. In the 65th minute, Riquelme scored from a free-kick which gave Boca a 2–1 lead before Fluminense again equalized. The second leg saw Fluminense defeat Boca Juniors 3–1, eliminating the Argentine side 5–3 on aggregate. Riquelme had scored four goals in the competition.

In October 2008, Boca Juniors centre-back Julio César Cáceres had a very public conflict with his teammate Riquelme, when during an interview on a Paraguayan radio station in Asunción, during his training with his national team, Cáceres questioned Riquelme’s motivation. He claimed that, “In some matches, he is apparently running and in others he is passive. He seems to be mentally saturated. He seems to have more motivation when he plays for his country.” Riquelme responded by saying, in a telephone interview on the Fox Sports cable channel, “He doesn’t know what I feel for the club. I take part in pre-match concentration just like the other players and I didn’t have a holiday because I chose to play in the [Olympic] Games. When we won the gold, I ran to the airport so I could play in the (Recopa Sudamericana 2008) final.” He added, “These things should be kept in the dressing-room, he’s broken all the codes of football.” After Boca won the Superclásico derby match over Buenos Aires rivals River Plate on 21 October 2008, Cáceres said that the conflict “has been left behind”, adding that the relationship between the two players had improved.

During the second leg of the 2008 Recopa Sudamericana, Riquelme scored a 91st minute free-kick to equalize the scores for Boca Juniors at 2–2 against Arsenal de Sarandí on 27 August 2008. Boca Juniors won the tie 5–3 on aggregate.

In August 2008, Riquelme was included as one of three over-age players, and also named captain, by Sergio Batista for Argentina’s 19-man squad for the 2008 Summer Olympics football tournament in Beijing. He had joined Javier Mascherano and Nicolás Pareja as the three over-aged players in the squad. Argentina were drawn in Group A against the Ivory Coast, Australia and Serbia. On 7 August, Riquelme played the full 90 minutes of Argentina’s opening group stage fixture as they defeated Ivory Coast 2–1. Three days later, Riquelme also played another 90 minutes in Argentina’s 1–0 victory against Australia on 10 August. Riquelme then rested on the bench in Argentina’s third group-stage fixture, giving the captain’s armband to Javier Mascherano, where they defeated Serbia 2–0 on 13 August to claim maximum points in the group and to finish in first place.

On 12 April 2010, Riquelme scored Boca’s third goal in the 47th minute of their 4–0 home victory against Arsenal de Sarandí.

Riquelme’s first appearance in the 2011–12 Argentine Primera División season came during the 2011 Torneo Apertura in a 1–1 home draw against Banfield on 12 June 2011. He scored his first goal of the 2011 Torneo Apertura in a 4–0 home victory against Unión de Santa Fé on 15 August; his was Boca’s third goal, coming in the 83rd minute. Boca finished in first place of the 2011 Torneo Clausura with 43 points, going undefeated in 19 league games. They had claimed the title for the first time in four years, securing qualification to the 2012 Copa Libertadores.

In 2011, Riquelme was called up to the Argentina national team by coach Alejandro Sabella for the Superclásico de las Américas, however he eventually withdrew his position from the squad due to injuries from club matches which would leave him unable to complete two games in a matter of days.

Riquelme’s first appearances in the 2011–12 Copa Argentina came in a 1–1 draw against Deportivo Santamarina on 2 February 2012. He assisted Facundo Roncaglia in scoring Boca’s equalizing goal of the match when he lobbed a free kick to Roncaglia, who headed the ball into the net in the 63rd minute. The match was decided via penalty shoot-out which Boca won 4–3. Riquelme’s first appearance of the 2012 Torneo Clausura came in a 2–0 home victory against Olimpo de Bahía Blanca on 10 February 2012, when he was substituted off of the field in the 79th minute for Cristian Chávez. Four days later, he debuted in the 2012 Copa Libertadores in a 0–0 away draw against Venezuelan side Zamora on 14 February. Riquelme scored his first goal of the 2012 Torneo Clausura in a 2–0 home victory against Newell’s Old Boys on 26 February; it was Boca’s second goal, coming in the 80th minute.

During the quarter-final stages of the Copa Libertadores, Boca were drawn against Fluminense. During the first leg in Buenos Aires on 17 May, Riquelme assisted Boca in scoring the only goal of the match when he played a ball through to Darío Cvitanich, who set up Pablo Mouche to score in the 51st minute of the 1–0 victory. Boca drew 1–1 in the second leg on 23 May, earning a 2–1 aggregate score and a spot in the semi-finals. On 3 June 2012, Boca faced Primera B Nacional second division club Deportivo Merlo in the semi-finals of the Copa Argentina. In the 57th minute of the match, Riquelme, initially taking a free-kick in front of goal, played a quick one-two with a teammate and curled the ball into the left side of the net, giving them a 1–0. Boca held on to the 1–0 lead until the 89th minute when Deportivo Merlo equalized. The match was eventually decided via penalty shoot-out which Boca won 5–4.

On 18 October 2012, it was reported that Riquelme’s agent, Daniel Bolotnicoff, had denied reports that any Australian A-League club had contacted him to show an interest in signing Riquelme, as he had been linked with Melbourne Heart and Western Sydney Wanderers. On 5 January 2013, it was reported that Riquelme nearly joined Major League Soccer (MLS) side Chivas USA when he was to follow former coach Carlos Bianchi in a trip to the United States, as the latter was going to be head coach of the MLS club. Bianchi was then announced as Boca’s first-team coach ten days later, which led to Riquelme’s reiteration that he would not re-join Boca Juniors as a player.

In January 2013, after much speculation that Riquelme was headed to join Palmeiras, it was announced by newly appointed club president Paulo Nobre that Palmeiras had to refrain from signing Riquelme due to financial terms and Riquelme’s asking salary.

On 26 January 2013, Riquelme confessed that he did not miss playing football and that his last options would be to play for Argentinos Juniors or Tigre. On 30 January 2013, it was officially reported that Argentinos Juniors president Luis Seguira had announced that the club would make an offer for Riquelme. On 31 January 2013, it was then reported that Riquelme had visited Tigre’s intendent, Sergio Massa, in order to discuss the possibility of his arrival at the club. On 3 February 2013, it was reported that, after various negotiations, Riquelme had accepted the offer to play for Tigre and that the discussion and confirmation of his contract was the only thing which remained to be done until his official signing with the club.

On 4 February 2013, it was reported that Riquelme had stated that he was prepared to return to Boca Juniors and that he had contacted Boca coach Carlos Bianchi that he would be available to return.

It was confirmed on 8 February 2013 that Riquelme would return to Boca Juniors. He was extremely decisive at the second match against Corinthians at the Copa Libertadores, scoring a goal from the midfield and knocking off the reigning FIFA Club World Cup champions.

On 30 March 2014, Riquelme scored a free kick in the Superclásico, but could not stop his team from losing 2–1 against River Plate.

On 17 July 2014, it was confirmed that Riquelme would sign with Argentinos Juniors. He scored his first goal with his new club on his first game against Boca Unidos.

On 23 January 2015, it was reported that Riquelme would travel to Asunción on Saturday 24 January to close the contract offer from Primera División Paraguaya club Cerro Porteño, which would be worth US$110,000 per month, a salary which Riquelme had asked to receive. It was later confirmed that Riquelme’s salary would make his contract the most expensive in the country.

On 25 January 2015, Riquelme officially announced his retirement from football via ESPN and ultimately gave thanks to Cerro Porteño.

On December 8, 2019, the formula headed by Jorge Amor Ameal, Mario Pergolini and Juan Román Riquelme was chosen with 52.84% of the votes, achieving the historical record in Argentine football of 20,045 votes in total. They take office on December 13, 2019.